The impact of mindfulness on working memory-related brain activation in breast cancer survivors with cognitive complaints.

PURPOSE: Cancer-related cognitive impairment (CRCI) has been associated with altered brain activation after chemotherapy in areas related to working memory. Hence, improving working memory capacity and associated brain activation might aid in the recovery of CRCI. In this study, we investigated the potential of a mindfulness-based intervention (MBI) to impact working memory-related brain activation. METHODS: Female breast cancer survivors reporting cognitive complaints (N=117) were randomized into a mindfulness (n=43; MBI), physical training (n=36; PT), or waitlist control condition (n=38; WL). Participants completed MRI scans before the intervention, immediately after, and three months post-intervention. Task-based functional MRI was used to measure differences between groups over time in working memory-related brain activation while performing a visual-verbal n-back task. RESULTS: Data of 83 participants (32/26/25 MBI/PT/WL) was included. Compared to the waitlist group, MBI participants showed reduced task-related activation in the right middle frontal and angular gyrus and increased activation in the right dorsal posterior cingulate cortex over time. Compared to the physical training group, MBI participants showed reduced brain activation in the bilateral superior parietal lobule and right dorsal anterior cingulate cortex over time. No differences between physical training and no intervention were identified. CONCLUSION: This study showed that an 8-week mindfulness-based intervention can significantly alter brain activation across brain regions involved in working memory, attentional control, and emotion processing during performance of a working memory task. This might aid in the recovery of CRCI. IMPLICATIONS FOR CANCER SURVIVORS: Mindfulness might alter brain activation patterns while performing a working memory task, which might ultimately aid in restoring higher order cognitive functions.

The Impact of Mindfulness on Functional Brain Connectivity and Peripheral Inflammation in Breast Cancer Survivors with Cognitive Complaints.

BACKGROUND: Cancer-related cognitive impairment (CRCI) has been linked to functional brain changes and inflammatory processes. Hence, interventions targeting these underlying mechanisms are needed. In this study, we investigated the effects of a mindfulness-based intervention on brain function and inflammatory profiles in breast cancer survivors with CRCI. METHODS: Female breast cancer survivors reporting cognitive complaints (n = 117) were randomly assigned to a mindfulness-based intervention (n = 43), physical training (n = 36), or waitlist control condition (n = 38). Region-of-interest (ROI) and graph theory analyses of resting state functional MRI data were performed to study longitudinal group differences in functional connectivity and organization in the default mode, dorsal attention, salience, and frontoparietal network. Additionally, bead-based immunoassays were used to investigate the differences in inflammatory profiles on serum samples. Measures were collected before, immediately after and three months post-intervention. RESULTS: No ROI-to-ROI functional connectivity changes were identified. Compared to no intervention, graph analysis showed a larger decrease in clustering coefficient after mindfulness and physical training. Additionally, a larger increase in global efficiency after physical training was identified. Furthermore, the physical training group showed a larger decrease in an inflammatory profile compared to no intervention (IL-12p70, IFN-γ, IL-1ß, and IL-8). CONCLUSION: Both mindfulness and physical training induced changes in the functional organization of networks related to attention, emotion processing, and executive functioning. While both interventions reduced functional segregation, only physical training increased functional integration of the neural network. In conclusion, physical training had the most pronounced effects on functional network organization and biomarkers of inflammation, two mechanisms that might be involved in CRCI.

The impact of mindfulness on cancer-related cognitive impairment in breast cancer survivors with cognitive complaints.

BACKGROUND: Interventions that target cancer-related cognitive impairment (CRCI) to improve the quality of life of cancer survivors are needed. In this study, the potential of a mindfulness-based intervention to reduce CRCI in breast cancer survivors, compared with physical training and a wait list control group, was investigated. METHODS: Breast cancer survivors with cognitive complaints (N = 117) were randomly allocated to a mindfulness (n = 43), physical training (n = 36), or wait list control condition (n = 38). Participants completed neuropsychological tests and questionnaires before the intervention, immediately after, and 3 months after intervention. The primary outcome measure was the change in cognitive complaints over time. Secondary outcomes were objective cognitive impairment and psychological well-being. All outcomes were compared between groups over time using linear mixed models, including participants with missing values. RESULTS: Of the 117 included participants, 96 completed the three assessments. Participants in the three groups reported decreased cognitive complaints after intervention, without group differences. There were no between-group differences in objective cognitive impairment after intervention compared with baseline. Compared with the wait list control group, participants reported increased mindfulness skills and reduced emotional distress after mindfulness and reduced emotional distress and fatigue after physical training. CONCLUSION: Contrary to the hypothesis, all groups reported an improvement in cognitive complaints over time. It is suggested that priming and acknowledgment of CRCI might alter the experience of cognitive impairment. Additionally, both mindfulness-based intervention and physical training can improve psychological well-being of breast cancer survivors with cognitive complaints.

Aligning Dentato-Rubro-Thalamic Tract and Subthalamic Nucleus Targets in a Patient with Comorbid Essential Tremor and Parkinson's Disease: Case Report.

Deep brain stimulation is an established treatment option for both essential tremor (ET) and Parkinson's disease (PD), although typically targeting different brain structures. Some patients are diagnosed with comorbid ET and PD. Selecting the optimal stimulation target in these patients is challenging. We present a patient with comorbid ET and PD in whom we used bilaterally a single parietal trajectory to align the dentato-rubro-thalamic tract and the subthalamic nucleus. Although parietal trajectories are challenging, we reached satisfactory outcomes for both conditions without complications. Single-electrode deep brain stimulation of the dentato-rubro-thalamic tract and the subthalamic nucleus through a parietal approach may represent a feasible treatment option in this patient group.

Effects of a mindfulness-based intervention on cancer-related cognitive impairment: Results of a randomized controlled functional magnetic resonance imaging pilot study.

BACKGROUND: Many breast cancer survivors suffer from cognitive complaints after cancer treatment, affecting their quality of life. The objective of this pilot study was to investigate the effect of a blended-care mindfulness-based intervention (MBI) on chemotherapy-related cognitive impairment and functional brain changes. Furthermore, correlations between changes in cognitive functioning and self-reported behavioral factors were investigated. METHODS: Breast cancer survivors (n = 33) who reported cognitive impairment were randomly allocated to a mindfulness condition (n = 18) or a waitlist control condition (n = 15). Patients completed questionnaires on cognitive impairment, emotional distress, and fatigue; neuropsychological tests; and resting-state functional magnetic resonance imaging before the start of MBI (time 1 [T1]), immediately after the completion of an 8-week MBI program (T2), and 3 months postintervention (T3). Resting-state functional connectivity was estimated in the default mode network, the dorsal and salience attention networks, and the frontoparietal network. Mixed model repeated-measures analysis was performed to test the intervention effect. RESULTS: Patients in the mindfulness condition exhibited significantly higher connectivity between the dorsal and salience attention networks after the mindfulness intervention compared with those in the control condition. MBI participants also had reduced subjective cognitive impairment, emotional distress, and fatigue. No intervention effect was observed on neurocognitive tests. CONCLUSIONS: MBI may induce functional brain changes in networks related to attention and may have a positive effect on subjective measures of cognitive impairment in breast cancer survivors. Therefore, MBI could be a suitable intervention to improve quality of life in this population and deserves further study in this context.

Baseline sensorimotor GABA levels shape neuroplastic processes induced by motor learning in older adults.

Previous research in young adults has demonstrated that both motor learning and transcranial direct current stimulation (tDCS) trigger decreases in the levels of gamma-aminobutyric acid (GABA) in the sensorimotor cortex, and these decreases are linked to greater learning. Less is known about the role of GABA in motor learning in healthy older adults, a knowledge gap that is surprising given the established aging-related reductions in sensorimotor GABA. Here, we examined the effects of motor learning and subsequent tDCS on sensorimotor GABA levels and resting-state functional connectivity in the brains of healthy older participants. Thirty-six older men and women completed a motor sequence learning task before receiving anodal or sham tDCS to the sensorimotor cortex. GABA-edited magnetic resonance spectroscopy of the sensorimotor cortex and resting-state (RS) functional magnetic resonance imaging data were acquired before and after learning/stimulation. At the group level, neither learning nor anodal tDCS significantly modulated GABA levels or RS connectivity among task-relevant regions. However, changes in GABA levels from the baseline to post-learning session were significantly related to motor learning magnitude, age, and baseline GABA. Moreover, the change in functional connectivity between task-relevant regions, including bilateral motor cortices, was correlated with baseline GABA levels. These data collectively indicate that motor learning-related decreases in sensorimotor GABA levels and increases in functional connectivity are limited to those older adults with higher baseline GABA levels and who learn the most. Post-learning tDCS exerted no influence on GABA levels, functional connectivity or the relationships among these variables in older adults.

A mindfulness-based intervention for breast cancer patients with cognitive impairment after chemotherapy: study protocol of a three-group randomized controlled trial.

BACKGROUND: Mindfulness has been applied to improve cancer care by enhancing psychological well-being. However, little is known about its impact on cognitive impairment experienced by cancer patients after chemotherapy. Mindfulness may be relevant in tackling cognitive impairment by decreasing emotional distress and fatigue, by decreasing inflammation, and by strengthening functional brain connectivity. The aim of the present study protocol is to evaluate the efficacy and mechanisms of a mindfulness-based intervention to reduce cognitive impairment in breast cancer patients after chemotherapy. METHODS/DESIGN: The present study is a three-arm, parallel-group, randomized controlled trial with assessments at baseline, 1 to 3 weeks after the intervention and at 3 months' follow-up. One hundred and twenty breast cancer patients who ended treatment a minimum of 6 months and a maximum of 5 years before, and who have cognitive complaints, will be enrolled. They will be randomized into one of the following three study arms: (1) a mindfulness-based intervention group (n = 40), (2) an active control condition based on physical training (n = 40), or (3) a treatment as usual (TAU) control group (n = 40). Both the mindfulness-based intervention and the active control condition consist of four group sessions (3 h for the mindfulness condition and 2 h for the physical training) spread over 8 weeks. The primary outcomes will be cognitive symptoms as measured by the Cognitive Failure Questionnaire and changes in functional brain connectivity in the attention network. Secondary outcomes will be (1) levels of emotional distress, fatigue, mindfulness, quality of life; (2) neurocognitive tests; (3) structural and functional brain changes using MR imaging and (4) measures of inflammation. DISCUSSION: The study will examine the impact of a mindfulness-based intervention on cognitive impairment in breast cancer patients. If the findings of this study confirm the effectiveness of a mindfulness-based program to reduce cognitive impairment, it will be possible to improve quality of life for ex-cancer patients. We will inform health care providers about the potential use of a mindfulness-based intervention as a non-pharmaceutical, low-threshold mental health intervention to improve cognitive impairment after cancer. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03736460. Retrospectively registered on 8 November 2018.

Functional brain changes in auditory phantom perception evoked by different stimulus frequencies.

Bayesian models of brain function such as active inference and predictive coding offer a general theoretical framework with which to explain several aspects of normal and disordered brain function. Of particular interest to the present study is the potential for such models to explain the pathology of auditory phantom perception, i.e. tinnitus. To test this framework empirically, we perform an fMRI experiment on a large clinical sample (n = 75) of the human chronic tinnitus population. The experiment features a within-subject design based on two experimental conditions: subjects were presented with sound stimuli matched to their tinnitus frequency (TF) as well as similar stimuli presented at a control frequency (CF). The responses elicited by these stimuli, as measured using both activity and functional connectivity, were then analyzed both within and between conditions. Given the Bayesian-brain framework, we hypothesize that TF stimuli will elicit greater activity and/or functional connectivity in areas related to the cognitive and emotional aspects of tinnitus, i.e. tinnitus-related distress. We conversely hypothesize that CF stimuli will elicit greater activity/connectivity in areas related to auditory perception and attention. We discuss our results in the context of this framework and suggest future directions for empirical testing.

Subcortical Volume Loss in the Thalamus, Putamen, and Pallidum, Induced by Traumatic Brain Injury, Is Associated With Motor Performance Deficits.

BACKGROUND: Traumatic brain injury (TBI) has been associated with altered microstructural organization of white matter (WM) and reduced gray matter (GM). Although disrupted WM organization has been linked to poorer motor performance, the predictive value of GM atrophy for motor impairments in TBI remains unclear. OBJECTIVE: Here, we investigated TBI-induced GM volumetric abnormalities and uniquely examined their relationship with bimanual motor impairments. METHODS: 22 moderate to severe TBI patients (mean age = 25.9 years, standard deviation [SD] = 4.9 years; time since injury = 4.7 years, SD = 3.7 years) and 27 age- and gender-matched controls (mean age = 23.4 years; SD = 3.8 years) completed bimanual tasks and a structural magnetic resonance imaging scan. Cortical and subcortical GM volumes were extracted and compared between groups using FreeSurfer. The association between bimanual performance and GM volumetric measures was investigated using partial correlations. RESULTS: Relative to controls, patients performed significantly poorer on the bimanual tasks and demonstrated significantly smaller total GM as well as overall and regional subcortical GM. However, the groups did not show significant differences in regional cortical GM volume. The majority of the results remained significant even after excluding TBI patients with focal lesions, suggesting that TBI-induced volume reductions were predominantly caused by diffuse injury. Importantly, atrophy of the thalamus, putamen, and pallidum correlated significantly with poorer bimanual performance within the TBI group. CONCLUSIONS: Our results reveal that GM atrophy is associated with motor impairments in TBI, providing new insights into the etiology of motor control impairments following brain trauma.

Cortical reorganization in an astronaut's brain after long-duration spaceflight.

To date, hampered physiological function after exposure to microgravity has been primarily attributed to deprived peripheral neuro-sensory systems. For the first time, this study elucidates alterations in human brain function after long-duration spaceflight. More specifically, we found significant differences in resting-state functional connectivity between motor cortex and cerebellum, as well as changes within the default mode network. In addition, the cosmonaut showed changes in the supplementary motor areas during a motor imagery task. These results highlight the underlying neural basis for the observed physiological deconditioning due to spaceflight and are relevant for future interplanetary missions and vestibular patients.

Characterizing the microstructural basis of "unidentified bright objects" in neurofibromatosis type 1: A combined in vivo multicomponent T2 relaxation and multi-shell diffusion MRI analysis.

INTRODUCTION: The histopathological basis of "unidentified bright objects" (UBOs) (hyperintense regions seen on T2-weighted magnetic resonance (MR) brain scans in neurofibromatosis-1 (NF1)) remains unclear. New in vivo MRI-based techniques (multi-exponential T2 relaxation (MET2) and diffusion MR imaging (dMRI)) provide measures relating to microstructural change. We combined these methods and present previously unreported data on in vivo UBO microstructure in NF1. METHODS: 3-Tesla dMRI data were acquired on 17 NF1 patients, covering 30 white matter UBOs. Diffusion tensor, kurtosis and neurite orientation and dispersion density imaging parameters were calculated within UBO sites and in contralateral normal appearing white matter (cNAWM). Analysis of MET2 parameters was performed on 24 UBO-cNAWM pairs. RESULTS: No significant alterations in the myelin water fraction and intra- and extracellular (IE) water fraction were found. Mean T2 time of IE water was significantly higher in UBOs. UBOs furthermore showed increased axial, radial and mean diffusivity, and decreased fractional anisotropy, mean kurtosis and neurite density index compared to cNAWM. Neurite orientation dispersion and isotropic fluid fraction were unaltered. CONCLUSION: Our results suggest that demyelination and axonal degeneration are unlikely to be present in UBOs, which appear to be mainly caused by a shift towards a higher T2-value of the intra- and extracellular water pool. This may arise from altered microstructural compartmentalization, and an increase in 'extracellular-like', intracellular water, possibly due to intramyelinic edema. These findings confirm the added value of combining dMRI and MET2 to characterize the microstructural basis of T2 hyperintensities in vivo.

The functional neuroanatomy of multitasking: combining dual tasking with a short term memory task.

Insight into the neural architecture of multitasking is crucial when investigating the pathophysiology of multitasking deficits in clinical populations. Presently, little is known about how the brain combines dual-tasking with a concurrent short-term memory task, despite the relevance of this mental operation in daily life and the frequency of complaints related to this process, in disease. In this study we aimed to examine how the brain responds when a memory task is added to dual-tasking. Thirty-three right-handed healthy volunteers (20 females, mean age 39.9 ± 5.8) were examined with functional brain imaging (fMRI). The paradigm consisted of two cross-modal single tasks (a visual and auditory temporal same-different task with short delay), a dual-task combining both single tasks simultaneously and a multi-task condition, combining the dual-task with an additional short-term memory task (temporal same-different visual task with long delay). Dual-tasking compared to both individual visual and auditory single tasks activated a predominantly right-sided fronto-parietal network and the cerebellum. When adding the additional short-term memory task, a larger and more bilateral frontoparietal network was recruited. We found enhanced activity during multitasking in components of the network that were already involved in dual-tasking, suggesting increased working memory demands, as well as recruitment of multitask-specific components including areas that are likely to be involved in online holding of visual stimuli in short-term memory such as occipito-temporal cortex. These results confirm concurrent neural processing of a visual short-term memory task during dual-tasking and provide evidence for an effective fMRI multitasking paradigm.

White matter lateralization and interhemispheric coherence to auditory modulations in normal reading and dyslexic adults.

Neural activation of slow acoustic variations that are important for syllable identification is more lateralized to the right hemisphere than activation of fast acoustic changes that are important for phoneme identification. It has been suggested that this complementary function at different hemispheres is rooted in a different degree of white matter myelination in the left versus right hemisphere. The present study will investigate this structure-function relationship with Diffusion Tensor Imaging (DTI) and Auditory Steady-State Responses (ASSR), respectively. With DTI we examined white matter lateralization in the cortical auditory and language regions (i.e. posterior region of the superior temporal gyrus and the arcuate fasciculus) and white matter integrity in the splenium of the corpus callosum. With ASSR we examined interhemispheric coherence to slow, syllabic-rate (i.e. 4 Hz) and fast, phonemic-rate (i.e. 20 Hz) modulations. These structural and functional techniques were applied in a group of normal reading adults and a group of dyslexic adults for whom previously reduced functional interhemispheric connectivity at 20 Hz has been reported (Poelmans et al. (2012). Ear and Hearing, 33, 134-143). This sample was chosen since it is hypothesized that in dyslexic readers insufficient hemispheric asymmetry in myelination might relate to their auditory and phonological problems. Results demonstrate reduced white matter lateralization in the posterior superior temporal gyrus and the arcuate fasciculus in the dyslexic readers. Additionally, white matter lateralization in the posterior superior temporal gyrus and white matter integrity in the splenium of the corpus callosum related to interhemispheric coherence to phonemic-rate modulations (i.e. 20 Hz). Interestingly, this correlation pattern was opposite in normal versus dyslexic readers. These results might imply that less pronounced left white matter dominance in dyslexic adults might relate to their problems to process phonemic-rate acoustic information and to integrate them into the phonological system.

Spinal cord stimulation modulates cerebral neurobiology: a proton magnetic resonance spectroscopy study.

INTRODUCTION: Although spinal cord stimulation (SCS) is a widely used treatment for chronic neuropathic pain secondary to spinal surgery, little is known about the underlying physiological mechanisms. METHODS: The primary aim of this study is to investigate the neural substrate underlying short-term SCS by means of (1)H MR spectroscopy with short echo time, in 20 patients with failed back surgery syndrome. RESULTS: Marked increase of γ-aminobutyric acid (GABA) and decrease in glucose in the ipsilateral thalamus were found between baseline situation without SCS and after 9' of SCS, indicating the key role of the ipsilateral thalamus as a mediator of chronic neuropathic pain. In addition, this study also showed a progressive decrease in glucose in the ipsilateral thalamus over time, which is in line with the findings of previous studies reporting deactivation in the ipsilateral thalamic region. CONCLUSIONS: The observation of GABA increase and glucose decrease over time in the ipsilateral thalamus may be the causal mechanism of the pain relief due to SCS or an epiphenomenon.

Does somatosensory discrimination activate different brain areas in children with unilateral cerebral palsy compared to typically developing children? An fMRI study.

Aside from motor impairment, many children with unilateral cerebral palsy (CP) experience altered tactile, proprioceptive, and kinesthetic awareness. Sensory deficits are addressed in rehabilitation programs, which include somatosensory discrimination exercises. In contrast to adult stroke patients, data on brain activation, occurring during somatosensory discrimination exercises, are lacking in CP children. Therefore, this study investigated brain activation with functional magnetic resonance imaging (fMRI) during passively guided somatosensory discrimination exercises in 18 typically developing children (TD) (age, M=14 ± 1.92 years; 11 girls) and 16 CP children (age, M=15 ± 2.54 years; 8 girls). The demographic variables between both groups were not statistically different. An fMRI compatible robot guided the right index finger and performed pairs of unfamiliar geometric shapes in the air, which were judged on their equality. The control condition comprised discrimination of music fragments. Both groups exhibited significant activation (FDR, p<.05) in frontoparietal, temporal, cerebellar areas, and insula, similar to studies in adults. The frontal areas encompassed ventral premotor areas, left postcentral gyrus, and precentral gyrus; additional supplementary motor area (SMA proper) activation in TD; as well as dorsal premotor, and parietal operculum recruitment in CP. On uncorrected level, p<.001, TD children revealed more left frontal lobe, and right cerebellum activation, compared to CP children. Conversely, CP children activated the left dorsal cingulate gyrus to a greater extent than TD children. These data provide incentives to investigate the effect of somatosensory discrimination during rehabilitation in CP, on clinical outcome and brain plasticity.

A tractography study in dyslexia: neuroanatomic correlates of orthographic, phonological and speech processing.

Diffusion tensor imaging tractography is a structural magnetic resonance imaging technique allowing reconstruction and assessment of the integrity of three dimensional white matter tracts, as indexed by their fractional anisotropy. It is assumed that the left arcuate fasciculus plays a crucial role for reading development, as it connects two regions of the reading network, the left temporoparietal region and the left inferior frontal gyrus, for which atypical functional activation and lower fractional anisotropy values have been reported in dyslexic readers. In addition, we explored the potential role of the left inferior fronto-occipital fasciculus, which might connect a third region of the reading network, the left ventral occipitotemporal region with the left inferior frontal gyrus. In the present study, 20 adults with dyslexia and 20 typical reading adults were scanned using diffusion tensor imaging, and the bilateral arcuate fasciculus and the left inferior fronto-occipital fasciculus were delineated. Group comparisons show a significantly reduced fractional anisotropy in the left arcuate fasciculus of adults with dyslexia, in particular in the segment that directly connects posterior temporal and frontal areas. This fractional anisotropy reduction might reflect a lower degree of myelination in the dyslexic sample, as it co-occurred with a group difference in radial diffusivity. In contrast, no significant group differences in fractional anisotropy were found in the right arcuate fasciculus or in the left inferior fronto-occipital fasciculus. Correlational analyses (controlled for reading status) demonstrated a specific relation between performance on phoneme awareness and speech perception and the integrity of left arcuate fasciculus as indexed by fractional anisotropy, and between orthographic processing and fractional anisotropy values in left inferior fronto-occipital fasciculus. The present study reveals structural anomalies in the left arcuate fasciculus in adults with dyslexia. This finding corroborates current hypotheses of dyslexia as a disorder of network connections. In addition, our study demonstrates a correlational double dissociation, which might reflect neuroanatomical correlates of the dual route reading model: the left arcuate fasciculus seems to sustain the dorsal phonological route underlying grapheme-phoneme decoding, while the left inferior fronto-occipital fasciculus seems to sustain the ventral orthographic route underlying reading by direct word access.

Theta-gamma dysrhythmia and auditory phantom perception.

Tinnitus is considered an auditory phantom percept analogous to phantom pain. Thalamocortical dysrhythmia has been proposed as a possible pathophysiological mechanism for both tinnitus and pain. Thalamocortical dysrhythmia refers to a persistent pathological resting state theta-gamma coupling that is spatially localized at an area where normally alpha oscillations predominate. Auditory cortex stimulation via implanted electrodes has been developed to treat tinnitus, targeting an area of activation on functional MR imaging elicited by tinnitus-matched sound presentation. The authors describe a case in which clinical improvement was correlated with changes in intracranial recordings. Maximal tinnitus suppression was obtained by current delivery exactly at the blood oxygen level-dependent activation hotspot, which colocalizes with increased gamma and theta activity, in contrast to the other electrode poles, which demonstrated a normal alpha peak. These spectral changes normalized when stimulation induced tinnitus suppression, both on electrode and source-localized electroencephalography recordings. These data suggest that thetagamma coupling as proposed by the thalamocortical dysrhythmia model might be causally related to a conscious auditory phantom percept.

Transcranial magnetic stimulation and extradural electrodes implanted on secondary auditory cortex for tinnitus suppression.

OBJECT: Tinnitus is a prevalent symptom, with clinical, pathophysiological, and treatment features analogous to pain. Noninvasive transcranial magnetic stimulation (TMS) and intracranial auditory cortex stimulation (ACS) via implanted electrodes into the primary or overlying the secondary auditory cortex have been developed to treat severe cases of intractable tinnitus. METHODS: A series of 43 patients who benefited transiently from 2 separate placebo-controlled TMS sessions underwent implantation of auditory cortex electrodes. Targeting was based on blood oxygen level-dependent activation evoked by tinnitus-matched sound, using functional MR imaging-guided neuronavigation. RESULTS: Thirty-seven percent of the patients responded to ACS with tonic stimulation. Of the 63% who were nonresponders, half benefited from burst stimulation. In total, 33% remained unaffected by the ACS. The average tinnitus reduction was 53% for the entire group. Burst stimulation was capable of suppressing tinnitus in more patients and was better than tonic stimulation, especially for noise-like tinnitus. For pure tone tinnitus, there were no differences between the 2 stimulation designs. The average pure tone tinnitus improvement was 71% versus 37% for noise-like tinnitus and 29% for a combination of both pure tone and noise-like tinnitus. Transcranial magnetic stimulation did not predict response to ACS, but in ACS responders, a correlation (r = 0.38) between the amount of TMS and ACS existed. A patient's sex, age, or tinnitus duration did not influence treatment outcome. CONCLUSIONS: Intracranial ACS might become a valuable treatment option for severe intractable tinnitus. Better understanding of the pathophysiological mechanisms of tinnitus, predictive functional imaging tests, new stimulation designs, and other stimulation targets are needed to improve ACS results.

Hippocampal malrotation in pediatric patients with epilepsy associated with complex prefrontal dysfunction.

PURPOSE: The cognitive consequences of hippocampal malrotation (HIMAL) were investigated in a matched control study of children with epilepsy. METHODS: Seven children with HIMAL were compared on a range of memory and attention tasks with 21 control children with epilepsy without temporal role pathology and 7 children with epilepsy and magnetic resonance imaging (MRI)-documented hippocampal sclerosis. In addition, in a statistical morphometric analysis, MRI studies from four children with HIMAL were compared to similar images of 20 age-matched typically developing control children. RESULTS: Although the task battery was sensitive to the memory deficit of the children with hippocampal sclerosis, it did not reveal memory impairment in the patients with HIMAL. In contrast, the patients with HIMAL were impaired on the attentionally more demanding dual tasks, compared to both the control and the hippocampal sclerosis group. The structural MRI analysis revealed morphometric abnormalities in the tail of the affected hippocampus, the adjacent neocortex, and the ipsilateral medial thalamus. The basal forebrain was bilaterally affected. Abnormalities in remote cortex were found in the ipsilateral temporal lobe, the contralateral anterior cingulate gyrus, and bilateral in the dorsolateral and lateral-orbitofrontal prefrontal cortex. DISCUSSION: Because the prefrontal cortical regions have been shown to be active during dual-task performance, the MRI results converge with the neuropsychological findings of impairment on these tasks. We conclude that HIMAL had no direct memory repercussions, but was secondary to subtle but widespread neurologic abnormalities that also affected morphology and functioning of the prefrontal cortex.

Visual presentation of phobic stimuli: amygdala activation via an extrageniculostriate pathway?

In the present study, event-related functional magnetic resonance imaging (fMRI) was used to examine the neural correlates of phobic fear by exposing spider phobic subjects to a visual presentation of spiders. In contrast to control subjects, spider phobics showed significantly increased activation in the amygdala and the pulvinar nucleus of the thalamus on the basis of region of interest (ROI) analysis. Furthermore, voxelwise analysis revealed increased activation related to phobia-specific pictures bilaterally in the anterior cingulate cortex, the left insular cortex and bilaterally in the supplementary motor area. These findings confirm the involvement of the amygdala in the processing of phobia-relevant stimuli as found earlier in a recent study. Moreover, the thalamus findings support the involvement of an extrageniculostriate pathway in the process of phobic fear.